Despite recent concern over the purported decline in sperm counts, there is little, if any, epidemiologic evidence regarding associations with environmental exposures or the timing of such exposures. Disruption of male reproductive function, and in particular decreased semen quality, is thought to be associated with exposure to endocrine active chemicals. To date, no direct evidence in humans either supports or refutes this conjecture. It is possible that exposure to such chemicals in utero and/or during early childhood may disrupt testicular development or development of related endocrine pathways, resulting in subtle disruption of male reproductive function. We propose to examine associations between prenatal exposures to one class of endocrine disruptors, the organochlorine compounds, and testicular and endocrine function in adult men including semen quality, fertility potential, current hormone concentrations and time to pregnancy. We also propose to examine whether such associations, if any, are mediated by disruptions of maternal thyroid function. From a follow up of the now adult members of the Columbia-Presbyterian cohort of the National Collaborative Perinatal Project and the Child Health and Development Study, we will obtain questionnaire data on fertility history, current lifestyle, socioeconomic status, and medical history, request a blood sample and request that the subject come to the clinic for two semen samples, approximately 3 weeks apart. Semen samples will be analyzed using a standard protocol at the University of California, Davis. Serum will be assayed for testosterone, estradiol, follicle stimulating hormone, luteinizing hormone and inhibin B. Stored, frozen prenatal sera will be assayed for organochlorine compounds, and for free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies. Statistical analysis will assess the associations between organochlorine compounds (total and in secondary analyses as specific congeners or groups of congeners) and each outcome variable. Other analyses will assess whether maternal thyroid function during pregnancy mitigates these associations. This study represents the first large systematic evaluation of prenatal exposures to organochlorine compounds and male reproduction and has important implications for basic science, public health and public policy. [unreadable] [unreadable]